N-(1-halo-1-nitroalkylthio)hydantoin



United States Patent 3,532,706 N-(l-HALO-1-NITROALKYLTHIO)HYDANTOIN Gustave K. Kohn and Joseph G. E. Fenyes, Berkeley,

Calif., assignors to Chevron Research Company, San Francisco, Calif., a corporation of Delaware No Drawing. Original application Sept. 7, 1965, Ser. No. 485,619, now Patent No. 3,468,905, dated Sept. 23, 1969. Divided and this application Dec. 4, 1968, Ser. No. 817,587

Int. Cl. C07d 49/32, 27/52, 51/30 US. Cl. 260-309.5 6 Claims ABSTRACT OF THE DISCLOSURE N-(l-halo-l-nitroalkylthio) dicarboximides wherein the alkyl group contains 2 to 6 carbon atoms and the halogen is of atomic number 17 to 35. Typical dicarboximides are N(l-chloro-l-nitroethylthio) phthalimide, N-(l-halo-lnitropropylthio) 5,5 dimethyl hydantoin, N,N-di-(1- chloro-l-nitropropylthio) uracil and 1,1-bis-(1-chloro-1- nitropropylthio) parabanic acid. These carboximides are fungicidal.

CROSS-REFERENCE TO RELATED APPLICATION wherein A is one of the following groups:

(1) 1,2-hexacarboeyclie group having from 0-3 sites of olefinic (aromatic unsaturation;

I (2) (R1)2C-NH wherein R is hydrogen or lower alkyl of from 1 to 6 carbons;

wherein R is hydrogen or lower alkyl, i.e., from 1 to 6 carbons, and B is a l-halo-l-nitroalkyl group in which the halogen is of atomic number 17 to 35 and the alkyl is of from 2 to 6 carbons, i.e., ethyl through heXyl.

The compounds in which A is hexacarbocyclic may be more explicitly described by the formula:

wherein X is halogen of atomic number 17 to 35, R is alkyl of from 1 to 5 carbons and the 1,2-cyclohexylene ring has from 0 to 3 sites of olefinic unsaturation, i.e., 1,2-phenylene, 1,2-dihydrophenylene, 1,2-tetrahydrophenylene and 1,2-hexahydrophenylene. Alternatively, the ring may be considered as phthalimide and derivatives thereof. In this case the ring could be phthalimide, dihydrophthalirnide, tetrahydrophthalimide and hexahydrophthalimide. The ring may be unsubstituted or singly substituted with a chloro, bromo, nitro or alkyl group such as methyl, ethyl, butyl, amyl, etc.

The dihydro derivative, that is, dihydrophthalimide, may be 1,3-, 1,4-, 2,4-, 3,5-, etc. The tetrahydro derivative may be 1-, 2-, 3-, or 4-. Preferred compounds are phthalimide and A -tetrahydrophthalimide.

Specific illustrations of hexacarboxylic compounds included within the above formula are:

The hydantoin compounds of this invention may be more rigorously represented by the formula wherein X is halogen of atomic number 17 to 35, i.e., chlorine or-bromine, R is alkyl of from 1 to 5 carbons and R is hydrogen or lower alkyl. Included among the lower alkyl groups are methyl, ethyl, propyl, butyl, amyl and hexyl. Preferred compounds are the 3-(1-halo-1- nitroalkyl) hydantoins.

Illustrative examples of some of the hydantoin compounds included in this invention are:

3-( l-chlorol-nitroethylthio) hydantoin,

3- 1 -bromol -nitrobutylthio) hydantoin,

3-( l-chloro-l-nitrohexylthio) hydantoin,

( 1-chloro-i-nitropropylthio) -5,5-dimethylhydantoin, l-bromo- 1 -nitroamylthio) -5-methylhydantoin,

( l-chloro- 1 -nitroethylthio -5 -ethy1hydantoin,

( 1-chloro-1-nitrobutylthio -5-butylhydantoin,

3- 3- 3- l-bromo-l-nitroethylthio)-5,5-dipropylhydantoin, etc.

Also, the pyrimidine compounds of this invention may be further defined by the structure wherein X is halogen of atomic number 17 to 35, R is alkyl of from 1 to 6 carbons and R is hydrogen or methyl. As derivatives of pyrimidine, these compounds may be termed 2,6-dioxypyrimidine or methyl-dioxypyrimidine, i.e., uracil or thymine.

Illustrative of the compounds in this grouping are: N,N di-(l chloro-l-nitroethylthio) uracil, N,N-di-(1- bromo 1 nitrobutylthio) uracil, N,N di-(l chloro-lnitrohexylthio) uracil, N,N di-(l-bromo-l-nitropropylthio) thymine, N,N di-(l-chloro-l-nitroethylthio) thymine, N,N-di-(l-chloro-l-nitrohexylthio) thymine, etc.

Examples of the di-(l-halo-l-nitroalkylthio) substituted parabanic acids of this invention are 1,3-bis-(1-chloro-lnitroethylthio) parabanic acid, 1,3-bis-(l-bromo-l-nitrobutylthio) parabanic acid, 1,3-bis-(l-chloro-l-nitrohexylthio) parabanic acid, etc.

The preparation of the unique N-(l-halo-l-nitroalkyl) dicarboximides of this invention may be carried out by reacting an alkali metal salt of the corresponding imide with a l-halo-l-nitroalkylsulfenyl halide. The imide may be contained in a suitable inert medium, such as an aromatic solvent, e.g., benzene, toluene, etc., an alcohol, e.g., methanol, ethanol, etc., or water. Furthermore, the imide may be used directly in the form of its alkali metal salt or the salt may be formed in situ.

The solution or suspension of the alkali metal salt of the imide is vigorously stirred, preferably at low temperature while the sulfenyl halide is added. The sulfenyl halide may be contained in a suitable inert solvent, such as petroleum ether or mixed hexanes, if desired. After a sufficient reaction period the product is isolated by filtration or by stripping off the solvent. The product then may, if desired, be recrystallized from a suitable solvent, such as methanol or an aromatic solvent.

The l-halo-l-nitroalkylsulfenyl halides used in the preparation of the compounds of this invention may be synthesized by reacting an alkali or alkaline earth metal salt of a primary nitroalkane with sulfur monochloride in the presence of an anhydrous, nonhydroxylic inert medium, such as ether, to form a bis-(l-nitroalkyl) disulfide and cleaving the disulfide with halogen, i.e., chlorine or bromine.

In specific illustration of the compounds of this invention and their method of preparation, the following examples are presented. These examples are offered as representative of the compounds falling within the scope of this invention and are not intended as limiting of the invention herein described.

EXAMPLE I A 4.2-gm. portion of the potassium salt of phthalimide mixed with 50 mls. ether was charged to a vessel. To this mixture was added 4.0 gm. l-chloro-l-nitroethylsulfenyl chloride in ether. This mixture was stirred for minutes after which the solids were filtered from the mixture. The solids were washed with water and dried, to leave 3 grns. N-(l-chloro 1 nitroethylthio) phthalimide. This compound was observed as a white solid which melted at l10-112 C. Its analysis was: percent Cl: theory-12.4, found-12.28; percent S: theory11.l5, found-ll.15.

EXAMPLE II A 5.0-g n. portion of the sodium salt of cis-A -tetrahydrophthalimide was charged to a vessel. To this mixture TABLE I Analyses Percent Cl Percent S Compound Theory Found Theory Found N-(1chlor0-1-nitropropylthio) phthalimide 11. 78 11. 0 10. 66 10. 22 N'(l-chloro-Lnitroethylthio)- cis-N-tetrahydrophthalimide- 12. 54 12. 65 11.02 10. 65

EXAMPLE III A 3.0-gm. portion of the monopotassium salt of hydantoin in ether was charged to a vessel. To this suspension 3.75 gm. 1 chloro-l-nitropropylsulfenyl chloride were added. The contents were stirred for 1 hour and allowed to stand for 3 days. The mixture was filtered and the solids were dried leaving 3.2 grns. 3-(1-chloro-1-nitropropylthio) hydantoin. It was observed as a white solid which melted at 157160 C. with decomposition. Its analysis was: percent Cl: theory-14.0, foundl4.33; percent S: theoryl2.65, found12.20.

EXAMPLE IV A 5.0-gm. portion of the sodium salt of uracil in water was charged to a vessel. This mixture was cooled in an ice bath and a hexane solution of 8.5 grns. of l-chloro-lnitro-propylsulfenyl chloride and 4.3 g. NaOH were added while the mixture was blended in a Waring Blendor. A

' gluey solid was formed. The water was decanted and the solids were slurried with hexane, filtered and dried, leaving 3.1 grns. product. The product, N,N-di-(l-chloro-lnitropropylthio) uracil melted at l29133 C. Its analysis was: percent Cl; theory16.91, found-14.55; percent S: theory-15.29, found15.19.

EXAMPLE V In the manner described in Example IV, N,N-di-(lchloro-l-nitroethylthio) uracil was prepared. It melted at -146 C. with decomposition and had the following analysis: percent Cl: theoryl9.l2, found18.63; percent S: theory16.4, foundl5.5l.

EXAMPLE VI A 5.0-gm. portion of the dipotassium salt of parabanic acid dissolved in ether was charged to a vessel. To this mixture Was added 10.0 gm. 1 chloro-l-nitropropylsul fenyl chloride. The contents were stirred for 1 hour and allowed to stand for 3 days. The solids were filtered off and the ether was stripped from the filtrate. The stripped filtrate was further distilled to 60 C. at 1.0 mm. Hg to give 4 grns. l,3-di-(l-chloro-l-nitropropylthio) para'banic acid. This product was observed to be a viscous orange oil.

These new compounds find use in the control and killing of fungi. A number of the invention compounds were evaluated for fungicidal effectiveness by means of the mycelial drop test. This test is designed to measure the fnngitoxic activity of fungicidal chemicals in terms of their degree of inhibition upon mycelial growth. Each compound to be tested was dissolved in acetone in dilutions as 6 indicated in Table II. Paper discs previously inoculated immediately incubated in a moist room for 24 hours at by impregnation with equal amounts of particular fungus 72-73 F. and a relative humidity of 95-97%, after which mycelium placed on potato dextrose agar medium were they were removed to a room with ambient temperatures treated by applying a precise and equal volume of each of in the range of 75-80 F. and a relative humidity of 85- these fungicidal solutions to their center. Following treat- 90% for 12 days. At the end of this incubation period, ment with the fungitoxic chemical, the discs were indisease readings were made by counting the local lesions cubated along with inoculated but untreated control on the primary leaves. These counts were compared with discs at ambient temperatures until such time that these a similarly inoculated but unsprayed control series to untreated control discs were filled with mycelial growth. determine the percentage of fungus control effected by Activity of the fungitoxic chemical tested was determined the fungitoxic chemical. The results appear in Table IV.

TABLE II Fungus mycelium percent inhibition Concentra- Compound tion, ppm. Pythium Fusarium Rhizoctonia Vertieilliurn N -(1-chloro-l-nitroethylthio)phthalimide N-(l-chloro-l-nitropropylthi)phthalimide N-(l-chloro-l-nitropr0p ylthio) -eis-A -tetrahydrophthalim de. N (l-chloro-l-nitroethylthio)-cis-A -tetrahydrophthalimid e... 3-(l-ehloro-l-nitropropylthio)hydantoin N,N-di-(l-chloro-l-nitropropylthio)urncil 1,3di-(l-chloro-l-nitropropylthio) parabanie acid by comparative measurements of radii of mycelial growth TABLE IV away from the edge of the disc in treated and untreated samples. From this comparison a percent inhibition of n ViVOBean rust growth area was determined. The results of this test for Compound; lf cent Con rol various compounds of this invention on the particular 3 )P 69 fungus mycelium are indicated in Table II. -1- f P PY )ph halimide 80 A number of the compounds were also tested for ef- N Y 01S A4 tetrafectiveness against spores by means of The Standard hydrophthahmide 88 Spore Slide-Germination Method for Determining Fungi- N b p py C15 A tetracidal Activity, described in the American Phyto athohYdI' Phthahinide 85 logical Society Journal, volume 33, pages 627-632(1943). 'Q P 9PY yf n 98 The method is designed to measure the fungitoxic activity p py fif 5 of fungicidal chemicals, their activity being expressed in 1,3 d1 p py )P terms of percent inhibition of germination of fungus d 96 s ores.

Each compound to be tested was dissolved in acetone Aslde from the speclfic formPlatlor} and appllfiiatlon to a concentration of 10 ppm. These solutions were then 40 of the Class compounds of the invention as represented pipetted into the wells of depression slides and allowed PY the regoing tests, thesecompounds maybe dispsered to dry. The wells were filled with a spore suspension of or upon other Inert hquld P sohfl earners, sllch as chamber overnight. A group of 100 spores was examined Inert C1335 Xylenes, T1 1e carflers P Y the and the number of spores germinated and not germinated of a dust: or used 1n conlul'lctlon Wlth a i l was counted and recorded to show the biological activity Wettlng agent t0 q a fit/enable p The fullgltolflc in terms of the percentage germination inhibition. Table compounds of lnvemlon y also be lated With III reports the results of this testing. other solvents, dispersing agents, or emulsifying agents.

TABLE III Organism percent inhibition 3-(l-chloro-l-nitropropylthio) hydantoin N, N -di-(l-ehloro-l-nitropropylthio) uraei Additionally, a similar sampling of the compounds of Further, these compounds may not only be applied alone this invention were tested for fungicidal activity in vivo. or in miXtllr s With other compounds of the disclosed In these tests, the chemicals were tested for the control clas but y l be used w ai qn with other of bean rust. According to this procedure, three replicate Ff toxlcams the formulatlon of funglcldal p pinto bean plants growing in a standard University of Smons- California soil mix, in the 3-triplicate state and approxi- The Compounds may be applied to any environmental mately 5 inches tall were sprayed at 15 psi. with an acetone solution of each of the compounds to be tested at a concentration of 500 ppm. These suspensions were made uniform by means of an inert wetting agent and suitable filler. The plants were dried at ambient greenhouse temso as to efiect the control of fungus and fungus diseases.

Pefatufes and then inoculated With a spray of PP As will be evident to those skilled in the art, various mately rediospofes P 1111- Of U romey'ces P modifim'tions on this invention can be made or followed, coli typica, the fungus causing bean rust. The plants were in the light of the foregoing disclosure and discussion,

tack. For example, the fungicidal compositions may be sprayed or otherwise applied directly to a plant or other host, may be applied to the plant seed, sprayed upon the soil or other plant environment, or used in similar ways area which is a host to fungus or suceptible to fungus at- 7 without departing from the spirit or scope of the dis- 3. A compound of claim 1 wherein R is methyl, ethyl, closure or from the scope of the following claims. propyl or amyl and R is hydrogen.

What is claimed is: 4. A compound of claim 1 wherein R is methyl. 1. Compound of the formula 5. A compound of claim 1 wherein one R is hydrogen 5 and the other is methyl, ethyl or butyl. O 6. 3-(1-chloro-1-nitroalkylthio)hydantoin wherein the H alkyl is of 2 to 6 cabron atoms. 11NC N09 N-S(|]R References Cited (R )zG-0 2 c 10 UNITED STATES PATENTS l) 2,553,775 5/1951 Hawley et al 260-3095 3,178,447 4/1965 Kohn 260-3095 wherein R is alkyl of 1 to 5 carbon atoms, X is halogen NATALIE TROUSOF Primary Examiner of atomic number 17 to 35 and R is hydrogen or lower 15 y US. Cl. X.R.

2. A compound of claim 1 wherein R 15 hydrogen. 7 

